Let-7b attenuates cisplatin resistance and tumor growth in gastric cancer by targeting AURKB

AbstractPlatinum drug treatment is one of the most predominant chemotherapeutic strategies for patients with gastric cancer (GC). However, the therapeutic effect is less than satisfactory, largely due to the acquired resistance to platinum drugs. Therefore, a better understanding of the underlying mechanisms can greatly improve the therapeutic efficacy of GC. In this study, we aimed to investigate the chemo-resistance related functions/mechanisms and clinical significance of glucose-regulated protein 75 (GRP75) in GC. Here, our data showed that compared with SGC7901 cells, the expression of GRP75 was markedly higher in cisplatin-resistance cells (SGC7901CR). Knockdown of GRP75 abolished the maintenance of mitochondrial membrane potential (MMP) and inhibited the nuclear factor erythroid-2-related factor 2 (NRF2), phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT), hypoxia-inducible factor 1α (HIF-1α), and c-myc, which resulted in blocking the activation of their downstream targets. These processes attenuated the anti-oxidation/apoptosis abilities and altered the metabolic reprogramming in SGC7901CR cells, leading to re-sensitizing these cells to cisplatin. However, overexpression of GRP75 in SGC7901 cells caused the opposite effects. A xenografts model confirmed the abovementioned results. In GC patients receiving platinum chemotherapy and a meta-analysis, a high level of GRP75 was positively associated with aggressive characteristics and poor prognosis including but not limited to gastrointestinal cancers, and was an independent predictor for overall survival. Collectively, our study indicated that GRP75 was involved in the cisplatin-resistance of GC and that GRP75 could be a potential therapeutic target for restoring the drug response in platinum-resistance cells and a useful additive prognostic tool in guiding clinical management of GC patients.

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Circ_002059 suppresses cell proliferation and migration of gastric cancer via miR-182/MTSS1 axis

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmab015 ◽

2021 ◽

Vol 53 (4) ◽

pp. 454-462

Author(s):

Ting Li ◽

Xiaomin Zuo ◽

Xiangling Meng

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Tumor Growth ◽

Luciferase Reporter ◽

Metastasis Suppressor ◽

Xenograft Tumor ◽

Cell Proliferation And Migration ◽

And Migration ◽

Xenograft Tumor Growth ◽

Proliferation And Migration

Abstract Circular RNAs (circRNAs) play either oncogenic or tumor suppressive roles in gastric cancer (GC). A previous study demonstrated that circ_002059, a typical circRNA, was downregulated in GC tissues. However, the role and mechanism of circ_002059 in GC development are still unknown. In this study, the levels of circ_002059, miR-182, and metastasis suppressor-1 (MTSS1) were examined by real-time quantitative polymerase chain reaction and western blot analysis. Cell proliferation and migration were evaluated by MTT assay and Transwell migration assay, respectively. The interactions between miR-182 and circ_002059 or MTSS1 were analyzed by dual-luciferase reporter assay. A GC xenograft model was established to validate the role of circ_002059 in GC progression in vivo. Overexpression of circ_002059 significantly inhibited, whereas knockdown of circ_002059 notably facilitated, cell proliferation and migration in GC cells. MTSS1 was found to be a direct target of miR-182 and circ_002059 upregulated MTSS1 expression by competitively sponging miR-182. Transfection with miR-182 mimic and MTSS1 silencing abated the inhibitory effect of circ_002059 on GC progression. Circ_002059 inhibited GC cell xenograft tumor growth by regulating miR-182 and MTSS1 expression. Collectively, Circ_002059 inhibited GC cell proliferation and migration in vitro and xenograft tumor growth in mice, by regulating the miR-182/MTSS1 axis.

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Expression of angiopoietin 1, 2, and their common receptor Tie 2 in human gastric cancer: implications for angiogenesis and tumor growth

The American Journal of Gastroenterology ◽

10.1016/s0002-9270(02)04597-5 ◽

2002 ◽

Vol 97 (9) ◽

pp. S42

Author(s):

H PARK

Keyword(s):

Gastric Cancer ◽

Tumor Growth ◽

Human Gastric Cancer ◽

Common Receptor ◽

Angiopoietin 1

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Interleukin-23A is associated with tumor growth in Helicobacter-pylori-related human gastric cancer

Cancer Cell International ◽

10.1186/s12935-014-0104-x ◽

2014 ◽

Vol 14 (1) ◽

Cited By ~ 13

Author(s):

Changming Liu ◽

Ying Zhang ◽

Jie Zhan ◽

Yuanyuan Zhao ◽

Qijun Wan ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Tumor Growth ◽

Human Gastric Cancer

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A novel design of HA-coated nanoparticles co-encapsulating plasmid METase and 5-Fu shows enhanced application in targeting gastric cancer stem cells

Biological Chemistry ◽

10.1515/hsz-2017-0208 ◽

2018 ◽

Vol 399 (3) ◽

pp. 293-303 ◽

Cited By ~ 3

Author(s):

Weifeng Yang ◽

Houting Zhang ◽

Lin Xin

Keyword(s):

Gastric Cancer ◽

Tumor Growth ◽

Precipitation Method ◽

Inhibition Effect ◽

Coated Nanoparticles ◽

Transmission Electron ◽

Targeted Drug ◽

Gastric Cancer Stem Cells ◽

Novel Design

AbstractNanoparticles (NPs) are recognized as an attractive vehicles for cancer treatment due to their targeted drug release. Gastric cancer is an important killer disease, and its therapy methods still need improvement. The NPs were prepared using a precipitation method, and were evaluated using transmission electron microscopy (TEM). MTT and Transwell assays were used to determine cell viability and apoptosis.In vivoexperiments were performed to validate the effects of NPs on tumor growth. Methioninase (METase)/5-Fu co-encaspulated NPs showed highest ζ size and lowest ζ potential than other NPs. The migration and tumorsphere formation ability of CD44(+) was stronger than CD44(−). The effects of METase/5-Fu co-encaspulated NPs on inhibition cell growth was stronger than that of 5-Fu encaspulated NPs, while HA coated NPs showed significant target ability than that NPs without HA. METase supplementation promoted the inhibition effect of 5-Fu on thymidylate synthetase (TS), as well as cell apoptosis. Thein vivoexperiments demonstrated that HA coated NPs significantly inhibited tumor growth. It was concluded that HA-coated NPs enhance the target ability, while METase/5-Fu co-encaspulated NPs promote the inhibition effects on tumor growth in gastric cancer.

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Doxorubicin Embedded into Nanofibrillated Bacterial Cellulose (NFBC) Produces a Promising Therapeutic Outcome for Peritoneally Metastatic Gastric Cancer in Mice Models via Intraperitoneal Direct Injection

Nanomaterials ◽

10.3390/nano11071697 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1697

Author(s):

Hidenori Ando ◽

Takashi Mochizuki ◽

Amr S. Abu Lila ◽

Shunsuke Akagi ◽

Kenji Tajima ◽

...

Keyword(s):

Gastric Cancer ◽

Drug Delivery ◽

Tumor Growth ◽

Bacterial Cellulose ◽

Anticancer Agents ◽

Intraperitoneal Administration ◽

In Vitro Release ◽

Xenograft Model ◽

Tumor Growth Inhibition

Natural materials such as bacterial cellulose are gaining interest for their use as drug-delivery vehicles. Herein, the utility of nanofibrillated bacterial cellulose (NFBC), which is produced by culturing a cellulose-producing bacterium (Gluconacetobacter intermedius NEDO-01) in a medium supplemented with carboxymethylcellulose (CMC) that is referred to as CM-NFBC, is described. Recently, we demonstrated that intraperitoneal administration of paclitaxel (PTX)-containing CM-NFBC efficiently suppressed tumor growth in a peritoneally disseminated cancer xenograft model. In this study, to confirm the applicability of NFBC in cancer therapy, a chemotherapeutic agent, doxorubicin (DXR), embedded into CM-NFBC, was examined for its efficiency to treat a peritoneally disseminated gastric cancer via intraperitoneal administration. DXR was efficiently embedded into CM-NFBC (DXR/CM-NFBC). In an in vitro release experiment, 79.5% of DXR was released linearly into the peritoneal wash fluid over a period of 24 h. In the peritoneally disseminated gastric cancer xenograft model, intraperitoneal administration of DXR/CM-NFBC induced superior tumor growth inhibition (TGI = 85.5%) by day 35 post-tumor inoculation, compared to free DXR (TGI = 62.4%). In addition, compared with free DXR, the severe side effects that cause body weight loss were lessened via treatment with DXR/CM-NFBC. These results support the feasibility of CM-NFBC as a drug-delivery vehicle for various anticancer agents. This approach may lead to improved therapeutic outcomes for the treatment of intraperitoneally disseminated cancers.

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